Summary of Study ST002696
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001668. The data can be accessed directly via it's Project DOI: 10.21228/M83H7N This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002696 |
| Study Title | ATP10A promotes endothelial cell insulin sensitivity and protects against female-specific dyslipidemia |
| Study Type | MS Untargeted Lipidomics |
| Study Summary | Endothelial dysfunction is strongly associated with metabolic and cardiovascular disease but how genetic and environmental factors intersect to promote disease progression remains elusive. Genetic association studies have linked ATP10A and closely related type IV P-type ATPases (P4-ATPases) to insulin resistance and vascular complications, such as atherosclerosis. Here, we generated Atp10A knockout mice and show that Atp10A deficiency results in female-specific dyslipidemia, independent of diet-induced obesity, characterized by elevated plasma triglycerides, free fatty acids and cholesterol, and altered HDL properties. We also observed increased circulating levels of several sphingolipid species and reduced levels of eicosanoids and bile acids. The Atp10A-/- mice also display hepatic insulin resistance without perturbations to whole-body glucose homeostasis. ATP10A is expressed in vascular and lymphatic endothelial cells, where reduced expression causes hyperactive insulin receptor signaling at basal insulin levels and an inability to properly respond to added insulin. This unique form of insulin resistance suggests that ATP10A promotes insulin receptor desensitization to maintain endothelial cell insulin sensitivity. These findings are clinically relevant because therapeutics that enhance ATP10A expression could improve vascular health and lipid metabolic profiles. |
| Institute | Vanderbilt University |
| Department | Chemistry |
| Laboratory | Center for Innovative Technology |
| Last Name | May |
| First Name | Jody |
| Address | 2301 Vanderbilt Place, Nashville, TN, 37235, USA |
| jody.c.may@vanderbilt.edu | |
| Phone | 615-875-8438 |
| Submit Date | 2023-04-20 |
| Num Groups | 2 |
| Total Subjects | 10 |
| Publications | submitted |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d, mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-05-24 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004369 | AN004370 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | Reversed phase | Reversed phase |
| Chromatography system | Agilent 6560 | Agilent 6560 |
| Column | Agilent ZORBAX RRHD Extend-C18 (50 x 2.1mm,1.8um) | Agilent ZORBAX RRHD Extend-C18 (50 x 2.1mm,1.8um) |
| MS Type | ESI | ESI |
| MS instrument type | QTOF | QTOF |
| MS instrument name | Agilent 6560 Ion Mobility | Agilent 6560 Ion Mobility |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | Ion Abundances | Ion Abundances |
Chromatography:
| Chromatography ID: | CH003275 |
| Chromatography Summary: | HPLC-IM-MS/MS on an Agilent 6560 mass spectrometer using a ZORBAX Extend-C18 RPLC column (Phase A: 0.1% formic acid and 10 mM NH4CHOO in water, Phase B: 0.1% formic acid and 10 mM NH4CHOO in 60:36:4 isopropanol:acetonitrile:water). |
| Instrument Name: | Agilent 6560 |
| Column Name: | Agilent ZORBAX RRHD Extend-C18 (50 x 2.1mm,1.8um) |
| Column Temperature: | 40 |
| Flow Gradient: | 70% B for 1 min, 70-86% B in 2.5 min, 86% B for 6.5 min, 86-100% B in 1 min, 100% B for 6 min, 100-70% B in 0.1 min, and 70% B for 1.9 min. |
| Flow Rate: | 300 ul/min |
| Solvent A: | Water (10mM Amm. Formate) 0.1% formic acid |
| Solvent B: | 60:36:4 IPA:ACN:H2O (10mM Amm. Formate) 0.1% formic acid |
| Chromatography Type: | Reversed phase |
